Evaluating cancer epidemiologic risk factors using multiple primary malignancies Journal Article


Authors: Kuligina, E.; Reiner, A.; Imyanitov, E. N.; Begg, C. B.
Article Title: Evaluating cancer epidemiologic risk factors using multiple primary malignancies
Abstract: BACKGROUND: Several authors have proposed the use of patients with double primary malignancies affecting the same or contralateral organ as a genetically enriched resource of cases for epidemiologic case-control studies in cancer. Such an approach is based on the assumption that the factors that increase the risk of a second primary are the same ones which influence the risk of a first primary. The advantages for statistical power are premised on the assumption that relative risks in survivors of a first primary cancer are similar to relative risks in the unaffected population. We explore these assumptions theoretically and empirically using published data from breast cancer studies involving bilateral breast cancer. METHODS: We conducted a literature review to identify case-control studies of variants in 4 genes known to affect breast cancer risk: CHEK2*1100delC; multiple variants in BRCA1 and BRCA2; and FGFR2 rs2981582. Summary odds ratios were obtained for each of 3 study designs: a conventional case-control design, the design comparing bilateral cases with unilateral controls, and the design comparing bilateral cases with population controls. RESULTS: The data show strong patterns of steadily increasing prevalence of risk factors from healthy controls to primary cases to bilateral cases, as expected. Relative risks in survivors of unilateral breast cancer are either the same as in the general population, or modestly attenuated. CONCLUSIONS: Patients with double primary malignancies are a very important underused resource for cancer epidemiologic investigation. Such patients are especially useful for broad genome-wide discovery studies, and for studies of rare, strong risk factors such as high penetrance genes. © 2010 by Lippincott Williams & Wilkins.
Keywords: primary tumor; gene mutation; case control study; case-control studies; cancer risk; cancer patient; methodology; breast cancer; prevalence; genetic variability; odds ratio; risk factors; breast neoplasms; brca1 protein; brca2 protein; risk factor; survivor; risk; population; genome; checkpoint kinase 2; cancer epidemiology; neoplasms, multiple primary; fibroblast growth factor receptor 2; epidemiologic studies
Journal Title: Epidemiology
Volume: 21
Issue: 3
ISSN: 1044-3983
Publisher: Lippincott Williams & Wilkins  
Date Published: 2010-05-01
Start Page: 366
End Page: 372
Language: English
DOI: 10.1097/EDE.0b013e3181cc8871
PUBMED: 20299982
PROVIDER: scopus
PMCID: PMC3142453
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: EPIDE" - "Source: Scopus"
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  1. Anne S Reiner
    248 Reiner
  2. Colin B Begg
    306 Begg